マダガスカルおよびケニア産薬用植物分布調査および医薬資源開発

2009 Fiscal Year Annual Research Report

• Project/Area Number: 18256001
• Research Institution: Tokushima Bunri University
• Principal Investigator: 浅川 義範 Tokushima Bunri University, 薬学部, 教授 (50033874)
• Co-Investigator(Kenkyū-buntansha): 福山 愛保 徳島文理大学, 薬学部, 教授 (70208990) ; 橋本 敏弘 徳島文理大学, 薬学部, 教授 (10075955) ; 豊田 正夫 徳島文理大学, 薬学部, 教授 (50122586) ; 長島 史裕 徳島文理大学, 薬学部, 准教授 (60228012) ; 伊藤 卓也 徳島文理大学, 薬学部, 助教 (90517484)
• Keywords: 薬学 / 薬用植物 / マダガスカル / 生理活性 / ビスビベンジル / 細胞毒性活性 / 抗インフルエンザ活性 / 微生物変換

Research Abstract

本研究はマダガスカルおよびケニアの薬用植物分布調査と人体に優しい医薬原料の供給および医薬品を創製することを目的とする。本年度は特に未利用苔類に焦点を当て研究を進めた。マダガスカル産ゼニゴケ類は環状ビスビベンジルであるmarchantin AおよびBがインフルエンザに対し強い抗ウイルス活性のあることを初めて見出した。marchantin Aは乾燥ゼニゴケ8kgから約80gから100g得られる。またハネゴケ類環状ビスビベンジルisoplagiochin類は臨床で用いられているパキシタキセルと同様の活性があることを再確認し,ジンガサゴケやウスバゼニゴケ類には抗肥満活性を示す同様のビスビベンジルriccardin Cを含むことも見出した。マダガスカル産薬用植物Cinnamosma属や苔類含有成分の探索を続行するとともに、これまで得られた化学成分との比較研究を行うためにマダガスカルと緯度が類似するボルネオやタイあるいは南半球タヒチ、ニューカレドニア、ニュージーランドなどに生息している苔類、アルゼンチン産シダ類の成分探索、ケニアから郵送されたWarburgia属薬用植物の成分研究を開始した。サワラゴケのherbertane型セスキテルペノイドは強い抗菌性、NO産生抑制活性を示すこと、Chandonanthus hirtellus Cembrane型ジテルペン含有し、それらがHL-60細胞毒性を示すこと、ボルネオ産アズマゴケはKB細胞毒活性のあるcostunolide, tulipinolide, 8α-acetoxyzaluzaninなどを含有すること、Hymenophyllum flabellatumは猛烈な辛味成分1-(2,4,6-trimethoxyphenyl)-but-2(E)-en-1-oneを含有することを見出し、またアルゼンチン産シダ類2種から新規phloroglucinol類を単離・構造決定し、これらの化合物は強い住血吸虫症中間宿主の巻貝の殺貝活性を示した。上記研究成果は国際シンポでの基調講演、国内の各種シンポジウムで発表するともに、原著、総説として発表した。マダガスカル産およびケニア産のCinnamosma属およびWarburgia ugandensisの各種のdrimane型セスキテルペノイド、苔類のherbertane型およびcuparene型セスキテルペン類のクロカビ属による微生物変換で5員環に酸素官能基の導入およびベンゼン環への直接水酸化を明らかにした。これらの成果は2冊の著書(英文総ページ560)としてCRCおよびElsevierから出版した。本研究代表者はマレーシア天然物協会から国際的に卓越した天然物化学研究業績を上げた研究者に授与されるJack Cannon国際賞を日本人として初めて受賞した。この内容は現地新聞、徳島新聞夕刊(2010年1月7日、朝刊同1月8日)に大きく取り上げられた。

Research Products

• [Journal Article] Biotransformation of sesquiterpenoids from liverworts by fungi and Mammals (2010)
  • Author(s): Asakawa, Y., Hashimoto, T., Noma, Y.
  • Journal Title: Nat.Prod.Commun. 5 Pages: 695-707
  • Peer Reviewed
• [Journal Article] Bazzania novae-zelandiae, Gackstromemia sp.and Dendromastigophora sp. (2010)
  • Author(s): Nagashima, F., Kuba, Y., Ogata A., Asakawa, Y., et al.
  • Journal Title: Nat.Prod.Res. 24 Pages: 68-75
  • Peer Reviewed
• [Journal Article] Microbial transformation of isopinocampheol and caryophyllene oxide (2010)
  • Author(s): Noma, Y., Hashimoto, T., Asakawa Y., et al.
  • Journal Title: Flavour F.J. 25 Pages: 161-170
  • Peer Reviewed
• [Journal Article] Chemosystematics of the liverworts collected in Borneo (2010)
  • Author(s): Ludwiczuk, A., Asakawa, Y.
  • Journal Title: Tropical Bryology 31 Pages: 33-42
  • Peer Reviewed
• [Journal Article] Volatile components from selected Tahitian liverworts (2009)
  • Author(s): Ludwiczuk, A., Komala., I., Asakawa, et al.
  • Journal Title: Nat.Prod.Commun. 4 Pages: 1387-1392
  • Peer Reviewed
• [Journal Article] Volatile constituents of Ocimum minimum herb cultivated in Portugal (2009)
  • Author(s): Skalicka-Wozniak, K., Asakawa Y., et.al.
  • Journal Title: Nat.Prod.Commun. 4 Pages: 1383-1386
  • Peer Reviewed
• [Journal Article] Pungent Aromatic Compounds from New Zealand Liverwort Hymenophyton flabellatum (2009)
  • Author(s): Toyota, M., Braggins, J., Omtsu, I., Asakawa, Y., et al.
  • Journal Title: Chem.Pharm.Bull. 57 Pages: 1015-1018
  • Peer Reviewed
• [Journal Article] Deciphering Pactamycin Biosynthesis and Engineered Production of New Pactamycin Analogues (2009)
  • Author(s): Ito, T., Roongsawang, Lu, W., et al.
  • Journal Title: ChemBioChem 10 Pages: 2253-2265
  • Peer Reviewed
• [Journal Article] Antimitotic activity of tow macrocyclic bis(bibenzyls), isoplagochins A and B from the liverwort Plagiochila fruticosa (2009)
  • Author(s): Morita, H., Tomizawa, Y., Hashimoto, T., Asakawa, Y.
  • Journal Title: Bioorg.Med.Chem.Lett. 19 Pages: 493-496
  • Peer Reviewed
• [Journal Article] Molluscicidal phloroglucinols from the fern Elaphoglossum piloselloides (2009)
  • Author(s): Socolsky, C., Asakawa, Y., Bardon A.
  • Journal Title: J.Nat.Prod. 72 Pages: 787-790
  • Peer Reviewed
• [Journal Article] Bryophytes : Bio- and Chemical Diversity, Bioactivity and Chemosystematics (2009)
  • Author(s): Asakawa, Y., Nagashima, F., Toyota, T., Hashimoto, T., Fukuyamaa Y., et al.
  • Journal Title: Heterocycles 77 Pages: 99-150
  • Peer Reviewed
• [Journal Article] Bio- and chemical diversity, bioactivity and chemosystematics (2009)
  • Author(s): Asakawa, Y., udwiczuk, A.
  • Journal Title: Malaysian J.Sci. 28 Pages: 229-257
  • Peer Reviewed
• [Journal Article] Novel selective ligands for free fatty acid receptors GPR120 and GPR40 (2009)
  • Author(s): Hara, T., Hashimoto, T., Asakawaa, Y., et al.
  • Journal Title: Naunyn-Schmiedeberg's Archives of Pharmacology 380 Pages: 247-255
  • Peer Reviewed
• [Journal Article] Biogenetic-like cyclization of denudatenone A to dolabellane-type diterpenoids Induced by samarium(II)Iodide : A ketyl-olefin radical coupling reaction forming five-membered carbocycles (2009)
  • Author(s): Sono, M., Hanaoaka, M., Hashimoto, T., Asakawa, Y., et al.
  • Journal Title: Synlett. 3 Pages: 469-471
  • Peer Reviewed
• [Presentation] In Antimycin 生合成遺伝子クラスターのクローニング (2010)
  • Author(s): 伊藤卓也、川西賢司、浅川義範
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 20100328-20100330
• [Presentation] コショウ科植物カバに含まれるカバピロン類の微生物変換 (2010)
  • Author(s): 橋本敏弘、野間義明, Agnieszka Ludwiczuk、浅川義範
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 20100328-20100330
• [Presentation] Recent Advances in Bryophytes ; Bio- and Chemical Diversity and Biological Activity (2010)
  • Author(s): 浅川義範
  • Organizer: Innovative Ideas in Natural Medicine Research : Perspective Views "Social Science, Molecular Biology, and Nano Materials
  • Place of Presentation: Toyama(Japan)
  • Year and Date: 20100218-20100219
• [Presentation] Phytochemistry of Bryophytes : Bio- and Chemical Diversity, Biological Activity and Chemosystematics (2009)
  • Author(s): 浅川義範
  • Organizer: Malaysian Natural Products International Seminar Silver Jubilee "Natural Products R&D : Leads from Nature"
  • Place of Presentation: Kuantan (Malaysia)
  • Year and Date: 20091123-20091124
• [Presentation] Biotransformation of Terpenoids : Highly Efficient Production of Functionalized Compounds from Secondary Metabolites by Microorganisms and Mammals (2009)
  • Author(s): 浅川義範
  • Organizer: Malaysian Natural Products International Seminar Silver Jubilee "Natural Products R&D : Leads from Nature"
  • Place of Presentation: Kuantan(Malaysia)
  • Year and Date: 20091123-20091124
• [Presentation] Bioactivity-Guided isolation of cytotoxic compounds in leaves of Alnus sieboldiana(Betulaceae) (2009)
  • Author(s): Ludwiczuk A., Saha A., Kuzuhara T., Asakawa Y.
  • Organizer: Malaysian Natural Products International Seminar Silver Jubilee "Natural Products R&D : Leads from Nature"
  • Place of Presentation: Kuantan(Malaysia)
  • Year and Date: 20091123-20091124
• [Presentation] Microbial Transformation of Globulol and Kavapyrones (2009)
  • Author(s): Noma, Y., Hashimoto, T., Ludwiczuk, A., Asakawa, Y., et al.
  • Organizer: Malaysian Natural Products International Seminar Silver Jubilee "Natural Products R&D : Leads from Nature"
  • Place of Presentation: Kuantan(Malaysia)
  • Year and Date: 20091123-20091124
• [Presentation] 食用キノコ類および地衣類より糖尿病予防薬の探索 (2009)
  • Author(s): 橋本敏弘、吉川和子、國土直樹, 浅川義範、平澤明、辻本豪三
  • Organizer: 第3回食品薬学シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 20091112-20091113
• [Presentation] 4員環構造を有するテルペノイドの微生物変換 (2009)
  • Author(s): 野間義明、浅川義範
  • Organizer: 第53回香料・テルペン・精油化学に関する討論会
  • Place of Presentation: 奈良
  • Year and Date: 20091107-20091109
• [Presentation] Terpenoids and Other Volatile Components from French Polynesian Liverworts (2009)
  • Author(s): Ludwiczuk, A., Komara, I., Asakawa, Y., et al.
  • Organizer: 第53回香料・テルペン・精油化学に関する討論会
  • Place of Presentation: 奈良
  • Year and Date: 20091107-20091109
• [Presentation] New Sesqui- and diterpenoids from the Liverwort, Chandonanthus hirstellus (2009)
  • Author(s): Komara, I., Ito, T., Nagashima, F., Ludwiczuk, A., Asakawa., et al.
  • Organizer: 第53回香料・テルペン・精油化学に関する討論会
  • Place of Presentation: 奈良
  • Year and Date: 20091107-20091109
• [Presentation] Prenylated Phloroglucinols from the fern, Elaphoglossum crassipes (2009)
  • Author(s): Socolsky, C., Asakawa, Y., Bardon, A.
  • Organizer: 第53回香料・テルペン・精油化学に関する討論会
  • Place of Presentation: 奈良
  • Year and Date: 20091107-20091109
• [Presentation] Searching of cytotoxic compounds in leaves of Alnus sieboldiana(Betulaceae) (2009)
  • Author(s): Ludwiczuk A., Saha A., Kuzuhara T., Asakawa Y.
  • Organizer: 日本生薬学会第56回年会
  • Place of Presentation: 京都
  • Year and Date: 20091002-20091003
• [Presentation] Phloroglucinols from the Argentine fern Elaphoglossum yungense (2009)
  • Author(s): Socolsky, C., Asakawa, Y.Bardon, A.
  • Organizer: 日本生薬学会第56回年会
  • Place of Presentation: 京都
  • Year and Date: 20091002-20091003
• [Presentation] Tahitian Liverworts-Rich Sources of Terpenoids and Other Volatiles (2009)
  • Author(s): Ludwiczuk, A., Komara, I., Pham, A., Asakawa, Y., et al.
  • Organizer: 40th International Symposium on Essential Oils
  • Place of Presentation: Savigliano(Italy)
  • Year and Date: 20090906-20090909
• [Presentation] Microbial Transformation of Isopinocampheol and Caryophyllene Oxide as Terpenoids with Four Carbon Ring (2009)
  • Author(s): Noma, Y., Hashimoto, T., Uehara, S., Asakawa, Y.
  • Organizer: 40th International Symposium on Essential Oils
  • Place of Presentation: Savigliano(Italy)
  • Year and Date: 20090906-20090909
• [Presentation] GC-MS Analysis of Volatile Components of Selected Liverworts and Japanese Medicinal Plants (2009)
  • Author(s): Mehmeti, V., Ito, T., Nagashima, F., Komala, I., Ludwiczuk, A., Buchbauer, G., Asakawa, Y.
  • Organizer: 40th International Symposium on Essential Oils
  • Place of Presentation: Savigliano(Italy)
  • Year and Date: 20090906-20090909
• [Presentation] Several Novel Biological Activities of Macrocyclic Bis(bibenzyls)from Liverworts (2009)
  • Author(s): 橋本敏弘, 浅川義範
  • Organizer: The 5^<th> Japan-Korea Young Scientists Meeting on Bioorganic and Natural Products Chemistry
  • Place of Presentation: Yugawara, (Japan)
  • Year and Date: 20090827-20090829
• [Presentation] New secoaromadendrane sesquiterpene lactone, cembrane and fusicoccane diterpenoids from the Tahitian liverwort Chandonanthus hirtellus (2009)
  • Author(s): Komala, I., Ito, T., Nagashima, Asakawa, Y.
  • Organizer: International Conference on Medicinal Chemistry
  • Place of Presentation: Bandung(Indonesia)
  • Year and Date: 20090806-20090808
• [Presentation] Terpenoids as the Chemical Markers of Cryptic Species within the Liver wort Conocephalum conicum (2009)
  • Author(s): Ludwiczuk, A., Asakawa, Y., Odrzykoski, I.J.
  • Organizer: TERPENET 2009. 9^<th> International Meeting : Biosynthesis and Function of Isoprenoids in Plants, Microorganisms and Parasites
  • Place of Presentation: Tokyo(Japan)
  • Year and Date: 20090525-20090529
• [Presentation] Identification and Functional Analysis of Terpene Cyclases Responsible for the Biosynthesis of Oil Body Components in the Liverwort Marchantia polymorpha (2009)
  • Author(s): Kenmoku, H., Takahashi, H., Noji, M., Toyota, M., Asakawa, Y.
  • Organizer: TERPENET 2009. 9^<th> International Meeting : Biosynthesis and Function of Isoprenoids in Plants, Microorganisms and Parasites
  • Place of Presentation: Tokyo
  • Year and Date: 20090525-20090529
• [Presentation] Terpenoids from the Tahitian Liverworts Chandonanthus hirtellus (2009)
  • Author(s): Komara, I., Ito, T., Nagashima, F., Asakawa, Y., et al.
  • Organizer: TERPENET 2009. 9^<th> International Meeting : Biosynthesis and Function of Isoprenoids in Plants, Microorganisms and Parasites
  • Place of Presentation: Tokyo
  • Year and Date: 20090525-20090529
• [Presentation] Chemosystematics of the Liverwort Conocephalum (2009)
  • Author(s): Ludwiczuk, A., Glowniak, K., Asakawa, Y., Odrzykoski, I.J.
  • Organizer: 徳島生物学会
  • Place of Presentation: 徳島
  • Year and Date: 2009-11-28
• [Book] Comprehensive Natural Products Chemistry II Chemistry and Biology (2010)
  • Author(s): Noma, Y., Asakawa, Y.
  • Total Pages: 132
  • Publisher: Elsevier(UK)
• [Book] Comprehensive Natural Products Chemistry II Chemistry and Biology (2010)
  • Author(s): Asakawa, Y., Noma, Y.
  • Total Pages: 162
  • Publisher: Elsevier(UK)
• [Book] Handbook of Essential Oils : Science, Technology and Applications (2009)
  • Author(s): Noma, Y., Asakawa, Y.
  • Total Pages: 151
  • Publisher: CRC Press(USA)
• [Book] Handbook of Essential Oils : Science, Technology and Applications (2009)
  • Author(s): Asakawa, Y., Noma, Y.
  • Total Pages: 104
  • Publisher: CRC Press(USA)